Ventilator-associated pneumonia due to Aeromonas hydrophila: A rare case report

Introduction. Aeromonas hydrophila is an opportunistic pathogen that can cause various infections, including pneumonia, in immunocompromised individuals. This case report presents a rare occurrence of ventilator-associated pneumonia (VAP) caused by Aeromonas hydrophila in an apparently non-immunocompromised patient. Case presentation. The patient exhibited signs and symptoms of VAP and was successfully treated with intravenous ciprofloxacin. The discussion highlights the characteristics of Aeromonas species, its virulence factors, risk factors for infection, and antibiotic profile. Conclusion. It emphasizes the need for awareness and suspicion of Aeromonas as a potential cause of VAP in ICU settings, as well as the importance of early detection and appropriate treatment for improved outcomes.


INTRODUCTION
Aeromonas hydrophila is considered an opportunistic infection causing soft-tissue infections, gastroenteritis, and sepsis in immunocompromised hosts [1].Aeromonas is an infrequently encountered microbial isolate in samples from the intensive care unit (ICU), often ignored as an incidental finding.It is multidrug-resistant and can lead to a fatal infection if left untreated [1].Here we report a rare case of ventilator-associated pneumonia (VAP) due to Aeromonas hydrophila, in an apparently nonimmunocompromised patient who responded to treatment.

CASE PRESENTATION
A 65 year female, known case of hypertension and chronic kidney disease (CKD) on medical management, was admitted elsewhere [day of illness 1 (DOI-1)], with chief complaints of gradually progressive shortness of breath and decreased urine output.She was intubated (DOI-6) in view of the shortness of breath, and initiated on renal replacement therapy (RRT) owing to anuria and rising creatinine levels.She was shifted to our hospital (DOI-20) for further management.At admission to ICU, the patient continued to remain on organ-supportive therapies including invasive mechanical ventilation, vasopressor, and renal replacement therapy.During the clinical course, the patient remained on mechanical ventilation due to significant neuromuscular weakness and recurrent infections including VAP with different etiologies, Pseudomonas aeruginosa (at DOI-48), and Klebsiella pneumoniae (at DOI-74) which were treated with intravenous imipenem and meropenem with colistin, respectively as per antimicrobial sensitivity reports.On DOI-81, the patient again had sign and symptoms of new-onset infection with raised total leucocyte count (TLC 16000/ cu.mm) and increased tracheal tube secretions, right lower lobe opacity in the Chest X-ray (CXR) (Fig. 1).High-resolution computed tomography (HRCT) thorax revealed diffuse centracinar and para septal emphysematous changes in both lungs likely infective (images not shown).
In microbiological processing of the sample obtained by bronchoalveolar lavage (BAL), direct staining from the BAL sample showed slender Gram-negative bacilli with pus cells.Culture was put up on Blood Agar and MacConkey Agar.On culture colonies were haemolytic greyish and circular on blood agar and showed non-lactose fermenting, flat, non-mucoid, spreading colonies on MacConkey agar that were catalase-positive and oxidase-positive (Fig. 2).It is a non-fastidious bacterium that grows well in ambient air after 16-20 h of incubation.Routine biochemical testing was done for presumptive identification of the isolate.Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) helped in pinpointing the species.The isolate was identified as Aeromonas hydrophila.The confidence level of MALDI-TOF for the detection of Aeromonas is 99 %.
Intravenous ciprofloxacin was started as per culture sensitivity, and the patient improved after 12 days of treatment (DOI-83 to 94), as evident clinically by a decrease in tracheal secretions, decreased TLC counts, and clearance of CXR opacities (Fig. 1).Subsequently, the patient was weaned off from the ventilator and discharged to home (DOI-120) in a clinically stable condition with continuing domiciliary care as per family members request with advice for continuing maintenance hemodialysis (twice weekly frequency), tracheostomy tube (due to inadequate power to clear respiratory secretions) and other supportive nursing care.In telephonic follow-up, family members informed about the death of the patient after 4 weeks of ICU discharge, however, family members did not reveal details about the terminal events.

DISCUSSION
Aeromonas are facultatively anaerobic, Gram-negative bacilli, which are oxidase-and catalase-positive [1].Initially, this genus was included in the family Vibrionaceae but at present put in a separate family Aeromonadacae based on deoxyribonucleic acid (DNA) hybridization and sequence analysis of 16S ribosomal ribonucleic acid (rRNA) studies [2].Aeromonas species are frequently isolated from fresh or brackish water, sewage, soil, and tap water in temperate or subtropical countries [3].Chlorinated water can also be containing Aeromonas [4].
Aeromonas has been regarded as an opportunistic agent that mainly causes gastroenteritis.Extra-intestinal infections caused by Aeromonas spp.include soft-tissue infections, arthritis, endocarditis, meningitis, urinary tract infections, pneumonia, and even sepsis in immunologically compromised hosts [5,6].The majority of Aeromonas-associated pneumonia has been reported after freshwater or saltwater near drowning [7][8][9].Though rare, it has been reported in empyema, lung abscesses, community-acquired as well as nosocomial pneumonia in immunocompromised patients [10].Malignancy and diabetes mellitus have been found to be common risk factors [5,11].Other significant risk factors include alcohol abuse and related hepatic disease, cardiovascular, cerebrovascular diseases, and chronic lung infections [12].In our case, prolonged illness with the need for organ supports like mechanical ventilation, renal replacement therapy, antimicrobial exposure were risk factors present for development of Aeromonas associated VAP.
Its involvement in nosocomial pneumonia has garnered attention due to its ability to colonize and persist in the respiratory tract.Cross-contamination due to improper hand hygiene, contaminated water used for humidification of airway tubings, and direct hematogenous transmission from the gut to lungs are major sources of Aeromonas pneumonia in critically ill patients.Additionally, for developing pneumonia, prolonged mechanical ventilation, underlying lung diseases, prior antibiotic therapy, and exposure to contaminated water sources are important risk factors in ICU settings.However in our case, ecological study was not carried out to rule out source.Also, no other cases had Aeromonas VAP during same time period in the ICU.
Virulence factors present in Aeromonas include lateral flagella, pilli, extracellular proteins like proteases, lipases, exotoxins, etc. [13].These factors aid in its colonization and invasion of the respiratory tract.Furthermore, its ability to form biofilms on endotracheal tubes and other medical devices contributes to its persistence in ICU patients.Studies have revealed infection with Aeromonas cause hypoxia-induced organ damage to severe necrotizing pneumonia with signs of pulmonary oedema, on histological examination.This is suggestive of the virulence of this pathogen and could explain the rapid clinical course and high mortality rate reaching up to 50 % as reported in the literature [14,15].
Aeromonas hydrophila VAP presents with symptoms similar to other types of VAPs, including fever, cough, purulent sputum, and radiographic evidence of pneumonia.Diagnosis typically involves obtaining respiratory samples for culture and identification of the organism.In our case, we could isolate the organism from the BAL sample which is the best possible minimally invasive respiratory sample and a very reliable one.
Aeromonas spp., including members of A. caviae, A. hydrophila, and A. veronii complexes, constitute the majority of susceptibility testing data.European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommends cefepime, ceftazidime, aztreonam, ciprofloxacin, levofloxacin and cotrimoxazole [16].Clinical and Laboratory Standards Institution (CLSI) recommends testing with piperacillin-tazobactam, cephems, carbapenems, aztreonam, aminoglycosides, cotrimoxazole, and fluoroquinolones for Aeromonas [17].Aeromonas strains are inherently resistant to ampicillin, amoxicillin-clavulanate, and cefazolin [18][19][20].Some strains may develop resistance due to inducible β-lactamases during treatment.Resistance to carbapenems can occur, colistin resistance has been reported due to mcr 3 gene [21].The Infectious Diseases Society of America (IDSA) recommends a combination of doxycycline with ciprofloxacin/ ceftriaxone for extraintestinal infections [22].Ciprofloxacin breakpoints include ≤0.25 mg l −1 as sensitive and >0.5 mg l −1 as resistant as per EUCAST [16].Treatment should be guided by clinical response [22], which was done in our case.Reasonable courses of therapy include 2 weeks of therapy for treatment of systemic infection.We used Kirby Bauer's disc diffusion method of antibiotic susceptibility testing.The isolated strain in our case was susceptible to amikacin, ciprofloxacin, ceftriaxone, ceftazidime, cefoperazone-sulbactam, imipenem, and meropenem.It was resistant to colistin.Ciprofloxacin is a good agent for pneumonia and the isolate we obtained was sensitive to it.So, the patient was treated with intravenous ciprofloxacin.
It has been estimated that the worldwide incidence of Aeromonas infection in humans varies in geographical location and developed to underdeveloped nations, ranging from 0.66 cases per million to 15 cases per million [14,23,24].Indian studies identified Aeromonas hydrophila in more than 30 % of the fish population under study [25].There are case reports of different species of Aeromonas causing VAP [26][27][28][29], single case of A. salmonicida has been reported in a study, and even a case of community acquired aspiration pneumonia due to A. hydrophila.Cases of A. hydrophila pneumonia due to leech therapy have also been documented [30].

CONCLUSION
Although it has long been known as an aquatic pathogen, Aeromonas hydrophila has become a pathognomonic contributor to VAP during prolonged illness.It is necessary to be aware of the possibility that A. hydrophila as the cause of VAP in the ICU settings.For managing A. hydrophila-associated VAP, a high index of suspicion, and focused antimicrobial stewardship with avoidance of contaminated sources are important, given the particular resistance pattern of the bacterium and high mortality rate.Several variables, like the patient's underlying health status, the promptness of the diagnosis, and the suitability of the antimicrobial therapy, can affect the prognosis of A. hydrophila VAP.If the infection is not properly treated, complications like sepsis, respiratory failure, and multi-organ dysfunction syndrome may develop.However, positive outcomes are possible with early detection, adequate treatment, and supportive care.

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Your submissions to our titles support the community -ensuring that we continue to provide events, grants and professional development for microbiologists at all career stages.(17).Aeromonasstrains are inherently resistant to ampicillin, amoxicillinclavulanate, and cefazolin (18)(19)(20).Some strains may develop resistance due to inducible β-lactamases during treatment.Resistance to carbapenems can occur.Colistin resistance has been reported due to mcr 3 gene (21).Infectious Diseases Society of America (IDSA) recommends combination of doxycycline with ciprofloxacin/ ceftriaxone for extraintestinal infections especially (22).Ciprofloxacin break points include </=0.25mg/l as sensitive and > 0.5 mg/l as resistant as per EUCAST (16).Treatment should be guided by clinical response (22), which was done in our case.Reasonable courses of therapy include two weeks of therapy for treatment of systemic infection.We used Kirby Bauer's disk diffusion method of antibiotic susceptibility testing.The isolated strain in our case was susceptible to Amikacin, Ciprofloxacin, Ceftriaxone, Ceftazidime, Cefoperazone-sulbactam, Imipenem, and Meropenem.It was resistant to colistin.Ciprofloxacin is a good agent for pneumonia and the isolate we obtained was sensitive to it.So, the patient was treated with intravenous ciprofloxacin.

Anonymous.
Date report received: 11 September 2023 Recommendation: Minor Amendment Comments: Description of the case -The case is described reasonably clearly, and the course of the disease process is clear to follow.The abstract and case description show that the patient responded to treatment but subsequently died outside the hospital.
No cause of death is given; was this associated with the chest infection (noting that she was discharged with a tracheostomy in place (lines 142-143) implying some residual respiratory disfunction) or from the underlying morbidities identified in the case (lines 123-124), or from some other cause?-In the abstract this is described as the 'first case of nosocomial pneumonia...' however in the discussion (lines 159-172) it is clear that ventilator-associated pneumonia (which is therefore nosocomial in origin) has been reported for Aeromonas species.Nosocomial Aeromonas hydrophila pneumonia has been previously reported (

Editor recommendation and comments https
://doi.org/10.1099/acmi.0.000672.v1.6 © 2023 de Dios R.This is an open access peer review report distributed under the terms of the Creative Commons Attribution License.Thank you very much for submitting your manuscript to Access Microbiology.It has now been reviewed by three experts, who have recommended a number of changes and suggestions.Please pay special attention to those recommending title changes, improvements to the Discussion section and updates in the bibliography.The reviewers have pointed out other previous cases of Aeromonas infections in the literatures, which will have to be considered and worth mentioned in this report.This is an open access peer review report distributed under the terms of the Creative Commons Attribution License.
(Baddour & Baselski, 1988h Med J. 1988; 81: 461-3; Plotkin & Scinico, Pa Med.1986; 89: 40-1) -these are old references and the authors may have thought that the isolate identifications may be questionable now when compared with updated routine laboratory methods.Could the authors address the fact that this is not the first description therefore of nosocomial pneumonia?-Severalriskfactorsarereported in the literature.To what extent were these risk factors present in this case, for example how immunocompromised was the patient as a consequence of the chronic renal disease, was there any e.g.liver, cardiovascular, cerebrovascular, or chronic lung diseases, cancer, MS,(Baddour & Baselski, 1988; Chao et.al., Eur J Clin Microbiol Infect Dis.2013; 32: 1069-75; Mukhopadhyay et.al.Yonsei Med J. 2003; 44: 1087-90)?-Whattreatmentwasgivenfor the Pseudomonas aeruginosa and Klebsiella pneumoniae (lines 131-132); could there have been selective pressure from this treatment to allow the Aeromonas infection to emerge?-How confident was the MALDI-TOF identification for the isolate (line 192-193)?Is this a commonly encountered organism in this laboratory or was any additional testing performed to confirm the identification?-Theisolate is reported as pan-sensitive and as resistant to colistin (lines 135-136); what is 'pan-sensitive' in this context?Current EUCAST breakpoints list only 6 agents for which specific breakpoints are available; CLSI M45 (2016) list more agents.What susceptibility testing method was used?Is there any MIC data available?Why was ciprofloxacin selected as the agent of choice?How the style and organization of the paper communicates and represents key findings -The organisation of the paper is generally clear, however the discussion section patient risk factors.I think this paper could be strengthened by incorporating some of these additional references, highlighting where appropriate how this case adds to the literature.Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?NoIs there a potential financial or other conflict of interest between yourself and the author(s)?NoIf this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?YesReviewer 2 recommendation and comments https://doi.org/10.1099/acmi.0.000672.v1.3 © 2023 behera b.This is an open access peer review report distributed under the terms of the Creative Commons Attribution License.The title can be amended by deleting the word "first case".Though uncommon, instances of Aeromonas in VAP cases are reported, e.g., Microbiological profile of ventilator-associated pneumonia among intensive care unit patients in tertiary Egyptian hospitals, J Infect Dev Ctries 2020; 14(2):153-161.doi:10.3855/jidc.12012.The pictorial description of microorganism and infection control aspects are not discussed and no clinical message is being conveyed by the manuscript.These aspects can be looked into.Please rate the quality of the presentation and structure of the manuscript SatisfactoryTo what extent are the conclusions supported by the data?Partially supportDo you have any concerns of possible image manipulation, plagiarism or any other unethical practices?NoIs there a potential financial or other conflict of interest between yourself and the author(s)?NoIf this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?Yes Reviewer 1 recommendation and comments https://doi.org/10.1099/acmi.0.000672.v1.4 © 2023 Lopez-Iniguez A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License.
does merge pathogenicity factors, antimicrobial susceptibilities, and clinical features into a single paragraph (lines 173-183) and I did think that this may have been improved by converting into separate paragraphs.I would have liked to have seen more discussion of risk factors for the acquisition and treatment outcomes for Aeromonas pneumonia.-There are occasions where the paper switches between post and present tenses when describing the clinical course; this can be corrected prior to publication.Aeromonas and other species names need italicising; again this can be corrected prior to publication.4. Literature analysis or discussion -A Pubmed search for 'Aeromonas hydrophila pneumonia' reveals a number of case reports and series which have not been referenced by the authors.These include nosocomial as well as community acquired infections, and together show a number of bijayini behera; AIIMS Bhubaneswar: All India Institute of Medical Sciences -Bhubaneswar, Microbiology, Bhubaneswar, INDIA https://orcid.org/0000-0002-4123-7990Date report received: 28 August 2023 Recommendation: Major Revision Comments: Alvaro Lopez-Iniguez; Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, Infectología, Vasco de Quiroga 15, Belisario Domínguez Sección XVI, Tlalpan, Mexico City., 14420, México, Mexico city, MEXICO